Ectopic Fat Accumulation in Distinct Insulin Resistant Phenotypes; Targets for Personalized Nutritional Interventions

Abstract

Cardiometabolic diseases are one of the leading causes for disability and mortality in the Western world. The prevalence of these chronic diseases is expected to rise even further in the next decades. Insulin resistance (IR) and related metabolic disturbances are linked to ectopic fat deposition, which is the storage of excess lipids in metabolic organs such as liver and muscle. Notably, a vicious circle exists between IR and ectopic fat, together increasing the risk for the development of cardiometabolic diseases. Nutrition is a key-determining factor for both IR and ectopic fat deposition. The macronutrient composition of the diet may impact metabolic processes related to ectopic fat accumulation and IR. Interestingly, however, the metabolic phenotype of an individual may determine the response to a certain diet. Therefore, population-based nutritional interventions may not always lead to the most optimal (cardiometabolic) outcomes at the individual level, and differences in the metabolic phenotype may underlie conflicting findings related to IR and ectopic fat in dietary intervention studies. Detailed metabolic phenotyping will help to better understand the complex relationship between diet and metabolic regulation, and to optimize intervention outcomes. A subgroup-based approach that integrates, among others, tissue-specific IR, cardiometabolic parameters, anthropometrics, gut microbiota, age, sex, ethnicity, and psychological factors may thereby increase the efficacy of dietary interventions. Nevertheless, the implementation of more personalized nutrition may be complex, costly, and time consuming. Future studies are urgently warranted to obtain insight into a more personalized approach to nutritional interventions, taking into account the metabolic phenotype to ultimately improve insulin sensitivity and reduce the risk for cardiometabolic diseases.

Ethnic differences in intrahepatic lipid and its association with hepatic insulin sensitivity and insulin clearance between men of black and white ethnicity with early type 2 diabetes

“…Despite relationships between IHL and whole‐body insulin resistance being commonly reported, the mechanisms that link the two are less well understood. Current investigations show an excess of liver fat leads to an accumulation of lipid intermediates causing hepatic mitochondrial dysfunction, inflammation and increased very low density lipoprotein ‐ triacylglycerol production which may result in hepatic and systemic insulin resistance . Our finding of IHL being inversely associated with basal hepatic insulin sensitivity and whole‐body insulin sensitivity, which reached significance in WE but not BWA men, may indicate the above detrimental effects of lipid intermediates occurring to a greater extent in WE men.…”

“…Current investigations show an excess of liver fat leads to an accumulation of lipid intermediates causing hepatic mitochondrial dysfunction, inflammation and increased very low density lipoprotein -triacylglycerol production which may result in hepatic and systemic insulin resistance. 14 whereas the South African women were normal glucose-tolerant. The disparities may also be a result of gender differences, as there is consistent evidence showing that the phenotype of T2D differs by gender within populations of African descent.…”

Oxygenation of adipose tissue: A human perspective

“…Hypertrophic WAT has been shown to have an impaired capacity to store meal‐derived fatty acids . As a consequence, more dietary lipids are diverted through the circulation to be stored in other tissues, which results in ectopic fat accumulation when lipid uptake exceeds lipid oxidation . The storage of excess lipids in non‐adipose tissues in obesity has important metabolic consequences, since this is closely associated with insulin resistance .…”

Transcriptome profiling reveals association of peripheral adipose tissue pathology with type-2 diabetes in Asian Indians

“…Therefore, in the present study we have conducted a cross-sectional microarray-based transcriptome profiling of 30 normal glucose tolerants and, 30 T2D individuals from their thigh subcutaneous adipose tissue. Our hypothesis is that the inability of protective adipose tissue in places like the thigh to store excess calories leads to ectopic fat deposition in the liver and muscle [10] contributing to the initiation or progression of T2D. In this study, we have also measured adipocyte size and counted the numbers of infilterating macrophages (total, anti-inflammatory and pro-inflammatory) and lymphocytes in femoral fat as a likely marker of pathologic adipose tissue.…”